With digital enhancements enabled by the device, such as zoom and higher contrast, some participants could read with acuity equivalent to 20/42 vision.
The results of the trial will be published Oct. 20 in the New England Journal of Medicine.
The device, called PRIMA, developed at Stanford Medicine, is the first eye prosthesis to restore functional sight to patients with incurable vision loss, giving them the ability to perceive shapes and patterns — also known as form vision.
“All previous attempts to provide vision with prosthetic devices resulted in basically light sensitivity, not really form vision,” said Daniel Palanker, PhD, a professor of ophthalmology and a co-senior author of the paper. “We are the first to provide form vision.”
The other senior author is José-Alain Sahel, MD, professor of ophthalmology at the University of Pittsburgh School of Medicine. The lead author is Frank Holz, MD, professor of ophthalmology at the University of Bonn in Germany.
The two-part device consists of a small camera, mounted on a pair of glasses, that captures images and projects them in real time via infrared light to a wireless chip in the eye. The chip converts the images into electrical stimulation, effectively taking the place of natural photoreceptors that have been damaged by disease.
PRIMA is the culmination of decades of development, prototypes, animal trials and a small first-in-human trial.
Palanker first imagined such a device 20 years ago, when he was working with ophthalmic lasers used to treat eye conditions. “I realized we should use the fact that the eye is transparent and deliver information by light,” he said.
“The device we imagined in 2005 now works in patients remarkably well.”
Replacing lost photoreceptors
Participants in the new trial had an advanced form of age-related macular degeneration, known as geographic atrophy, that gradually erodes central vision. Over 5 million people globally are affected by the condition, and it is the most common cause of irreversible blindness among the elderly.
Macular degeneration destroys light-sensitive photoreceptors in the center of the retina, the thin neural tissue in the back of the eye that converts light into electrical signals that then travel to the brain. But most patients retain some photoreceptor cells that allow peripheral vision as well as the retinal neurons that relay information from photoreceptors.
The new device takes advantage of what is preserved.
The 2-by-2-millimeter chip that receives images is implanted in the part of the retina where photoreceptors have been lost. The chip is sensitive to infrared light projected from the glasses, unlike real photoreceptors that respond only to visible light.
“The projection is done by infrared because we want to make sure it’s invisible to the remaining photoreceptors outside the implant,” Palanker said.
The design means patients can use their natural peripheral vision along with the prosthetic central vision, which helps with orientation and navigation.
“The fact that they see simultaneously prosthetic and peripheral vision is important because they can merge and use vision to its fullest,” Palanker said.
Because the chip is photovoltaic, meaning it needs only light to generate electric current, it can operate wirelessly and be implanted under the retina. Previous eye prostheses required an external power source and a cable running out of the eye.
Reading again
The new trial included 38 patients older than 60 who had geographic atrophy due to age-related macular degeneration and worse than 20/320 vision in at least one eye.
Four to five weeks after implantation of the chip in one eye, patients began using the glasses. Though some patients could make out patterns immediately, all patients’ visual acuity improved over months of training.
“It may take several months of training to reach top performance — which is similar to what cochlear implants require to master prosthetic hearing,” Palanker said.
Of the 32 patients who completed the one-year trial, 27 could read and 26 demonstrated clinically meaningful improvement in visual acuity, which was defined as the ability to read at least two additional lines on a standard eye chart. On average, participants’ visual acuity improved by 5 lines; one improved by 12 lines.
The participants used the prosthesis in their daily lives to read books, food labels and subway signs. The glasses allowed them to adjust contrast and brightness and magnify up to 12 times. Two-thirds reported medium to high user satisfaction with the device.
Nineteen participants experienced side effects, including ocular hypertension (high pressure in the eye), tears in the peripheral retina and subretinal hemorrhage (blood collecting under the retina). None were life-threatening, and almost all resolved within two months.
Future visions
For now, the PRIMA device provides only black-and-white vision, with no shades in between, but Palanker is developing software that will soon enable the full range of grayscale.
“Number one on the patients’ wish list is reading, but number two, very close behind, is face recognition,” he said. “And face recognition requires grayscale.”
He is also engineering chips that will offer higher resolution vision. Resolution is limited by the size of pixels on the chip. Currently, the pixels are 100 microns wide, with 378 pixels on each chip. The new version, already tested in rats, may have pixels as small as 20 microns wide, with 10,000 pixels on each chip.
Palanker also wants to test the device for other types of blindness caused by lost photoreceptors.
“This is the first version of the chip, and resolution is relatively low,” he said. “The next generation of the chip, with smaller pixels, will have better resolution and be paired with sleeker-looking glasses.”
A chip with 20-micron pixels could give a patient 20/80 vision, Palanker said. “But with electronic zoom, they could get close to 20/20.”
Researchers from the University of Bonn, Germany; Hôpital Fondation A. de Rothschild, France; Moorfields Eye Hospital and University College London; Ludwigshafen Academic Teaching Hospital; University of Rome Tor Vergata; Medical Center Schleswig-Holstein, University of Lübeck; L’Hôpital Universitaire de la Croix-Rousse and Université Claude Bernard Lyon 1; Azienda Ospedaliera San Giovanni Addolorata; Centre Monticelli Paradis and L’Université d’Aix-Marseille; Intercommunal Hospital of Créteil and Henri Mondor Hospital; Knappschaft Hospital Saar; Nantes University; University Eye Hospital Tübingen; University of Münster Medical Center; Bordeaux University Hospital; Hôpital National des 15-20; Erasmus University Medical Center; University of Ulm; Science Corp.; University of California, San Francisco; University of Washington; University of Pittsburgh School of Medicine; and Sorbonne Université contributed to the study.
The study was supported by funding from Science Corp., the National Institute for Health and Care Research, Moorfields Eye Hospital National Health Service Foundation Trust, and University College London Institute of Ophthalmology.
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